Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder

Objective: High prevalence of vitamin D deficiency was previously reported in children with Autism Spectrum Disorder (ASD), but little is known about the efficacy of vitamin D3 treatment in ASD, although data from pilot studies seem promising. We hypothesized that serum vitamin D levels are reduced in ASD and correlate with the severity of disease. Also, we hypothesized that vitamin D3 treatment may be beneficial for a considerable portion of children with ASD.

Methods: In total, 215 children with ASD and 285 healthy control children were recruited in our study. Thirty seven of 215 ASD children received vitamin D3 treatment. The Autism Behaviour Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to assess autism symptoms. High-performance liquid chromatography was used to assess the serum 25-hydroxyvitamin D [25(OH) D] level. Evaluations of ABC, CARS, and serum 25(OH) D levels were performed before and after 3 months of treatment.

Results: Serum levels of 25(OH) D were significantly lower in ASD children than typically developing children. Levels of serum 25(OH) D were negatively correlated with ABC total scores and language subscale scores. After vitamin D3 supplementation, symptom scores were significantly reduced on the CARS and ABC. In addition, the data also suggest that treatment effects were more pronounced in younger children with ASD.

Conclusion: Vitamin D deficiency might contribute to the aetiology of ASD. Supplementation of vitamin D3, which is a safe and cost-effective form of treatment, may significantly improve the outcome of some children with ASD, especially younger children (identifier ChiCTR-CCC-13004498).

Clinical Trial Registration: The trial ‘Association of Polymorphisms of Vitamin D Metabolism-Related Genes With Autism and the Treatment of Autism with Vitamin D’ has been registered at www.chictr.org/cn/proj/show.aspx? proj=6135 (identifier ChiCTR-CCC-13004498).     

维生素D在孤独症谱系障碍中作用的研究进展

孤独症谱系障碍(ASD)是影响儿童健康的严重公共问题之一,以社交沟通障碍、兴趣或活动范围狭窄以及重复刻板行为为特征。近年来越来越多的研究显示,ASD患儿维生素D(VitD)水平明显低于同龄健康儿童,VitD缺乏可能与ASD的发病机制相关。本文就VitD与ASD的相关研究进行综述。     

维生素D在孤独症谱系障碍中作用的研究进展

孤独症谱系障碍(ASD)是影响儿童健康的严重公共问题之一,以社交沟通障碍、兴趣或活动范围狭窄以及重复刻板行为为特征。近年来越来越多的研究显示,ASD患儿维生素D(VitD)水平明显低于同龄健康儿童,VitD缺乏可能与ASD的发病机制相关。本文就VitD与ASD的相关研究进行综述。     

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children

Objectives: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited.

Methods: We performed a case–controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children.

Results: Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30?ng/ml) participated in the open label trial. They received vitamin D3 (300?IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span.

Conclusion: Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40?ng/ml.

Trial registration number: UMIN-CTR Study Design: trial Number: R000016846.     

25(OH)Vitamin D Deficiency and Calcifediol Treatment in Pediatrics

Vitamin D is essential for the normal mineralization of bones during childhood. Although diet and adequate sun exposure should provide enough of this nutrient, there is a high prevalence of vitamin D deficiency rickets worldwide. Children with certain conditions that lead to decreased vitamin D production and/or absorption are at the greatest risk of nutritional rickets. In addition, several rare genetic alterations are also associated with severe forms of vitamin-D-resistant or -dependent rickets. Although vitamin D3 is the threshold nutrient for the vitamin D endocrine system (VDES), direct measurement of circulating vitamin D3 itself is not a good marker of the nutritional status of the system. Calcifediol (or 25(OH)D) serum levels are used to assess VDES status. While there is no clear consensus among the different scientific associations on calcifediol status, many clinical trials have demonstrated the benefit of ensuring normal 25(OH)D serum levels and calcium intake for the prevention or treatment of nutritional rickets in childhood. Therefore, during the first year of life, infants should receive vitamin D treatment with at least 400 IU/day. In addition, a diet should ensure a normal calcium intake. Healthy lifestyle habits to prevent vitamin D deficiency should be encouraged during childhood. In children who develop clinical signs of rickets, adequate treatment with vitamin D and calcium should be guaranteed. Children with additional risk factors for 25(OH)D deficiency and nutritional rickets should be assessed periodically and treated promptly to prevent further bone damage.     

Effect of Vitamin D and Docosahexaenoic Acid Co-Supplementation on Vitamin D Status,Body Composition,and Metabolic Markers in Obese Children: A Randomized,Double Blind,Controlled Study

Obese children are at high risk of developing vitamin D deficiency. Omega-3 polyunsaturated fatty acids and their derivatives might have a beneficial effect on vitamin D status of obese children, due to their anti-inflammatory action, and increasing its absorption. This multicenter, randomized, double-blind controlled study aims to investigate the effect of vitamin D and docosahexaenoic acid (DHA) co-supplementation for six months on vitamin D status, body composition, and metabolic markers of obese children with vitamin D deficiency. A total of 108 children were enrolled and 73 children completed the study: 33 were supplemented with an oral dose of 500 mg of DHA and 1200 IU/day of vitamin D3 and 41 were supplemented with 1200 IU/day of vitamin D3 + wheat germ oil. At the end of the study, more than 50% of the subjects improved their vitamin D status. However, co-supplementation was not more effective than vitamin D plus wheat germ oil. Fat mass percentage was significantly reduced, and body mass index improved in both groups, even if all the subjects were still obese at the end of the study. Children receiving both vitamin D and DHA presented a higher increase of DHA levels that could be relevant to prevent inflammatory-associated complications of obesity, but they had no effect on vitamin D levels.     

The Association between Vitamin D Status and Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis

The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant studies to estimate whether vitamin D status was related to ASD in this work. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to include eligible studies. A random-effects model was applied to pool overall estimates of vitamin D concentration or odds ratio (OR) for ASD. In total, 34 publications involving 20,580 participants were identified in this present study. Meta-analysis of 24 case–control studies demonstrated that children and adolescents with ASD had significantly lower vitamin D concentration than that of the control group (mean difference (MD): −7.46 ng/mL, 95% confidence interval (CI): −10.26; −4.66 ng/mL, p < 0.0001, I² = 98%). Quantitative integration of 10 case–control studies reporting OR revealed that lower vitamin D was associated with higher risk of ASD (OR: 5.23, 95% CI: 3.13; 8.73, p < 0.0001, I² = 78.2%). Analysis of 15 case–control studies barring data from previous meta-analysis reached a similar result with that of the meta-analysis of 24 case–control studies (MD: −6.2, 95% CI: −9.62; −2.78, p = 0.0004, I² = 96.8%), which confirmed the association. Furthermore, meta-analysis of maternal and neonatal vitamin D showed a trend of decreased early-life vitamin D concentration in the ASD group (MD: −3.15, 95% CI: −6.57; 0.26, p = 0.07, I² = 99%). Meta-analysis of prospective studies suggested that children with reduced maternal or neonatal vitamin D had 54% higher likelihood of developing ASD (OR: 1.54, 95% CI: 1.12; 2.10, p = 0.0071, I² = 81.2%). These analyses indicated that vitamin D status was related to the risk of ASD. The detection and appropriate intervention of vitamin D deficiency in ASD patients and pregnant and lactating women have clinical and public significance.     

0~14岁儿童25-羟维生素D 水平调查与分析

目的 了解0~14岁儿童体内维生素D的营养状况, 为本地区儿童合理补充维生素D提供科学依据。方法 对广州中山大学附属第三医院儿童保健门诊进行常规体检的1 000例0~14岁的儿童采用酶联免疫法检测血清25-羟维生素D[25-hydroxy vitamin D, 25-(OH)D]水平。结果 25-(OH)D缺乏及不足者634例(63.4%);25-( OH) D水平充足者366例(36.6%)。0~1和1~2岁组儿童血清25-(OH)D水平最高, 2岁后儿童随着年龄增长逐渐下降(P＜0.01)。0~7岁男、女童血清 25-(OH)D水平差异无统计学意义(P＞0.05), 但在7~14岁组儿童男、女比较差异有统计学意义(P＜0.01)。血清25-(OH)D水平夏＞秋＞春＞冬, 冬季维生素D缺乏或不足的检出率为70.29%, 高于其他季节(P＜0.05)。结论 0~14岁儿童 25-(OH)D平均水平低下, 普遍存在维生素D缺乏或不足, 特别是在冬季和年长儿童。     

儿童反复呼吸道感染与血清维生素A、D、E水平的相关性研究

目的 探讨儿童反复呼吸道感染与患儿血清维生素A、D、E水平的相关性研究,为临床治疗提供科学依据。方法 选取2015年在长春市儿童医院参加儿童保健,近3个月反复呼吸道感染病史患儿66例为病例组;选取前来参加儿童保健的健康儿童66例为对照组。用高效液相色谱法检测维生素A、D、E的水平。结果 不同年龄组儿童患反复呼吸道感染疾病的差异有统计学意义(χ²=13.516,P=0.001),病例组儿童血清维生素A水平和缺乏率明显低于对照组(t=3.536,P=0.001;χ²=16.901,P=0.000),病例组儿童血清25(OH)D、维生素E水平和缺乏率与对照组比较差异无统计学意义(P>0.05)。结论 反复呼吸道感染可能与维生素A缺乏有关,建议加强营养教育和宣传,指导儿童家长进行科学喂养,定期监测维生素A、D、E水平并适量补充维生素。     

儿童维生素D缺乏对血清铁蛋白的影响

目的 了解东莞市儿童维生素D(VD)缺乏现状,研究VD缺乏对血清铁蛋白的影响。方法 选取2016年11月－2018年4月间在东莞市儿童医院体检的6个月~14岁儿童,检测血清铁蛋白及VD浓度,采用SPSS24.0进行统计分析。结果 VD降低的比例为34.73%,而婴幼儿组、学龄前组和学龄组的VD降低的比例分别为19.75%、65.45%和77.78%,储存铁减少的比例为22.42%。VD正常组血清铁蛋白浓度高于VD不足组及VD缺乏组(F=6.21,P=0.002)。年龄增大(OR=0.312,95%CI:0.233~0.419,P＜0.001)为储存铁减少的保护因素,VD不足(OR=1.377,95%CI:1.109~1.710,P＝0.004)为储存铁减少的危险因素。结论 本院健康体检儿童VD缺乏的比例较高,且随着年龄增大而升高,VD缺乏为血清铁蛋白降低的危险因素之一。临床工作中有必要延长VD制剂补充的年限,同时,在铁缺乏或者补充铁剂疗效欠佳的病例,建议同时检测VD浓度。     

哮喘儿童血清维生素D水平与肺功能相关性分析

目的 了解支气管哮喘急性发作期儿童的血清25羟维生素D[25(OH)D]水平,分析其与肺功能、血清IgE之间的相关性,以进一步发现维生素D与儿童哮喘的关系。方法 调查2015-2016年潍坊市妇幼保健院50名哮喘急性发作儿童和50名健康儿童,用酶联免疫法检查血清25(OH)D和IgE浓度,用肺功能仪检测急性发作患儿的用力肺活量(FVC)、第1秒最大呼气量(FEV₁)、第1秒最大呼气率(FEV₁/FVC%)。分析两组儿童血清25(OH)D含量差异,及哮喘组患儿血清25(OH)D水平与急性发作严重程度的相关性。结果 支气管哮喘急性发作期儿童血清25(OH)D浓度为(19.54±7.85)ng/ml,显著低于对照组(25.28±3.48) ng/ml,差异有统计学意义(t=5.679,P<0.05)。血清25(OH)D水平与急性发作儿童的FVC、FEV₁及FEV₁/FVC%之间呈正相关(r=0.375、0.339、0.384),与IgE之间呈负相关(r=-0.534)。结论 哮喘儿童存在维生素D缺乏,血清25(OH)D与哮喘发作的严重程度存在关联。     

儿童血清维生素A、D、E水平与肺炎支原体肺炎相关性的临床研究

目的 研究儿童血清维生素A、D、E水平与肺炎支原体肺炎的相关性,为临床防治提供指导。方法 选取肺炎支原体肺炎住院治疗患儿415例为支原体肺炎组,儿保科非呼吸道感染儿童431例为对照组。分别检测两组儿童血清维生素A、D、E水平。结果 支原体肺炎组血清维生素A、D、E平均值均明显低于对照组(P<0.01);维生素A缺乏例数明显高于对照组(P<0.01),亚临床维生素A缺乏例数与对照组相比差异无统计学意义(P>0.05);维生素D缺乏及不足例数均明显高于对照组(P<0.01);维生素E缺乏例数明显高于对照组(P<0.01)。结论 维生素A、D、E缺乏与肺炎支原体肺炎的发病相关,特别是缺乏维生素A,补充维生素A、D、E有可能对预防肺炎支原体肺炎反复发作有益,其具体机制有待于进一步探讨。     

Incidence and characteristics of vitamin D deficiency rickets in New Zealand children: a New Zealand Paediatric Surveillance Unit study

Objective: To investigate the incidence and characteristics of vitamin D deficiency rickets in New Zealand (NZ). Methods: Prospective surveillance among paediatricians of Vitamin D Deficiency Rickets was conducted by the New Zealand Paediatric Surveillance Unit (NZPSU) for 36 months, from July 2010 to June 2013, inclusive. Inclusion criteria were: children and adolescents <15 years of age with vitamin D deficiency rickets (defined by low serum 25‐hydroxyvitamin D and elevated alkaline phosphatase levels, and/or radiological rickets). Results: Fifty‐eight children with confirmed vitamin D deficiency rickets were identified. Median age was 1.4 (range 0.3–11) years, 47% were male, and 95% of the children were born in NZ; however, the majority of the mothers (68%) were born outside NZ. Overall annual incidence of rickets in children aged <15 years was 2.2/100,000 (95%CI 1.4–3.5); with incidence in those <3 years being 10.5/100,000 (95%CI 6.7–16.6). Skeletal abnormalities, poor growth and motor delay were the most common presenting features, with hypocalcaemic convulsion in 16% of children. Key risk factors identified were: darker skin pigment, Indian and African ethnicity, age <3 years, exclusive breast feeding, and southern latitude, particularly when combined with season (winter/spring). Of the patients reported, none had received appropriate vitamin D supplementation. Conclusions: Vitamin D deficiency rickets remains a problem for NZ children. Key risk factors remain similar to those identified in the international literature. Preventative targeted vitamin D supplementation, as per existing national guidelines, was lacking in all cases reported. Implications: Vitamin D deficiency rickets is the most significant manifestation of vitamin D deficiency in growing children. To reduce the incidence of this disease among those at high risk, increasing awareness and implementation of current public health policies for targeted maternal, infant and child supplementation are required.     

The ODIN project: Development of food‐based approaches for prevention of vitamin D deficiency throughout life

Vitamin D deficiency has significant implications for human health throughout life and impacts on healthy growth and development and successful ageing. Persistent knowledge gaps are barriers to developing and implementing a safe and effective public health strategy to prevent vitamin D deficiency and maintain nutritional adequacy throughout the year. The European Commission‐funded ODIN project (Food‐based solutions for optimal vitamin D nutrition and health through the life cycle) will provide the evidence base to prevent vitamin D deficiency and improve nutrition and public health through food. ODIN will deliver the first internationally comparable dataset of vitamin D status and report the prevalence of vitamin D deficiency across Europe for the first time. In a series of dose‐response randomised controlled trials, ODIN will estimate dietary requirements for vitamin D in pregnant women, children, adolescents and adults of South Asian and East African origin resident in Northern European countries. Using clinically validated, disease‐specific cohorts with standardised 25(OH)D data, ODIN will investigate associations between vitamin D status and perinatal outcomes, atopic disease and bone growth in children, and cardiovascular and mortality risk in older adults. We will publish estimates of the distribution of vitamin D intake and serum 25(OH)D concentration resulting from changes in vitamin D in the food supply, accounting for latitude, sun exposure and diet. Utilising advanced food production systems and targeted animal and human feeding studies, ODIN will propose safe, novel and effective food‐based strategies to eradicate vitamin D deficiency that are inclusive, sustainable and affordable.     

Live Longer with Vitamin D?

The global burden of vitamin D deficiency or insufficiency is of great concern for public health. According to recent studies, vitamin D deficiency is an important etiological factor in the pathogenesis of many chronic diseases. Whether or not there is a connection between 25-hydoxyvitamin D (25(OH)D) status and overall mortality is a matter of considerable debate. A new meta-analysis confirmed that low 25(OH)D levels were associated with a significant increased risk for all-cause mortality. Individuals with severe vitamin D deficiency have almost twice the mortality rate as those with 25(OH)D level ≥ 30 ng/mL, (≥75 nmol/L). Unlike previous meta-analyses which suggested that serum 25(OH)D > 50 ng/mL was associated with increased mortality, this new analysis found that there was no increased risk even when 25(OH)D levels were ≥70 ng/mL. In general, closer attention should be paid to vitamin D deficiency in medical and pharmaceutical practice than has been the case hitherto. The results of these studies are consistent with the recommendation to improve the general vitamin D status in children and adults by means of a healthy approach to sunlight exposure, consumption of foods containing vitamin D and supplementation with vitamin D preparations.     

An Update on Vitamin D Deficiency Status in Malaysia

Vitamin D is essential for maintaining serum calcium levels, ensuring sufficient bone mineralization, immunomodulatory properties, and a protective effect on the cardiovascular system, renal disease, cancer, as well as in pregnancy. Vitamin D deficiency is prevalent worldwide, and it is not related to a country’s development index. However, the data on vitamin D deficiencies are primarily taken from out-of-date, small-scale studies on target age groups or specific diseases, rather than from large-scale, population-based surveys. In Malaysia, for the past 16 years, studies were conducted involving adult men and women, pregnant women, postmenopausal women, adolescent, and children especially with specific diseases such as spina bifida, epilepsy, chronic liver disease, and atopic dermatitis. Only a few large surveys were conducted involving children and adolescents. Across the specific target population studied, vitamin D deficiency and insufficiency were seen particularly among females, Indians, and those of Malay ethnicity. This is related to widely known causes of vitamin D deficiency such as skin type (melanin) and sun avoidant lifestyles that include covering clothes, largely practiced by Malay Muslims in Malaysia. Other related causes or the high-risk groups are breastfed infants, the elderly, the obese, those on medications, and those characterized by fat malabsorption and geophysical factors. Vitamin D deficiency can be managed with pharmacological or non-pharmacological approaches, depending on the severity. The objective is to raise serum vitamin D to a normal level, hence, relieving the symptoms and reducing the adverse health outcomes. Despite no clear guidelines in treating vitamin D deficiency in Malaysia, this condition can be prevented with taking adequate vitamin D in food resources, sun exposure, or supplementation. Special attention should be given to high-risk groups including infants, obese patients, and the elderly.     

Vitamin D and Pancreatitis: A Narrative Review of Current Evidence

Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.     

健康学龄前351名儿童25-羟维生素D水平及影响因素

目的 了解上海市学龄前儿童的维生素D水平并分析其影响因素,为防治该地区维生素D缺乏提供理论依据。方法 随机抽取上海市浦东新区3家幼儿园共351名3～6岁学龄前儿童(男:185名,女:166名),采用液相色谱串联质谱法(LC-MS/MS)测定测血清25-羟维生素 D[25-(OH)D]水平,并通过标准问卷获得相关影响因素数据。结果 受试学龄前儿童血清25-羟维生素 D[25-(OH)D]的平均水平为(28.14±6.70) ng/ml。维生素D缺乏[25-(OH)D＜20 ng/ml]为35例(10.0％),维生素D适宜水平(20～100 ng/ml)为316例(90.0%)。多因素分析结果显示维生素D制剂补充频率低及大年龄组(≥6岁)是学龄前儿童25-(OH)D缺乏的高危因素(P＜0.05)。结论 年龄和维生素D制剂补充与学龄前儿童维生素D水平明显相关,大年龄组(≥6岁)儿童维生素D制剂补充率相对较低。针对目前学龄前儿童仍存在维生素D缺乏的情况,应该加强儿童保健的科普教育,结合个体情况提高维生素D的补充率,同时增加儿童户外活动,促进学龄前儿童健康。     

Vitamin D Deficiency and the Lung: Disease Initiator or Disease Modifier?

Vitamin D deficiency is a global public health problem and has been associated with an increased incidence and severity of many diseases including diseases of the respiratory system. These associations have largely been demonstrated epidemiologically and have formed the basis of the justification for a large number of clinical supplementation trials with a view to improving disease outcomes. However, the trials that have been completed to date and the ongoing experimental studies that have attempted to demonstrate a mechanistic link between vitamin D deficiency and lung disease have been disappointing. This observation raises many questions regarding whether vitamin D deficiency is truly associated with disease pathogenesis, is only important in the exacerbation of disease or is simply an indirect biomarker of other disease mechanisms? In this review, we will briefly summarize our current understanding of the role of vitamin D in these processes with a focus on lung disease.     

健康学龄前351名儿童25-羟维生素D水平及影响因素

目的 了解上海市学龄前儿童的维生素D水平并分析其影响因素,为防治该地区维生素D缺乏提供理论依据。方法 随机抽取上海市浦东新区3家幼儿园共351名3～6岁学龄前儿童(男:185名,女:166名),采用液相色谱串联质谱法(LC-MS/MS)测定测血清25-羟维生素 D[25-(OH)D]水平,并通过标准问卷获得相关影响因素数据。结果 受试学龄前儿童血清25-羟维生素 D[25-(OH)D]的平均水平为(28.14±6.70) ng/ml。维生素D缺乏[25-(OH)D＜20 ng/ml]为35例(10.0％),维生素D适宜水平(20～100 ng/ml)为316例(90.0%)。多因素分析结果显示维生素D制剂补充频率低及大年龄组(≥6岁)是学龄前儿童25-(OH)D缺乏的高危因素(P＜0.05)。结论 年龄和维生素D制剂补充与学龄前儿童维生素D水平明显相关,大年龄组(≥6岁)儿童维生素D制剂补充率相对较低。针对目前学龄前儿童仍存在维生素D缺乏的情况,应该加强儿童保健的科普教育,结合个体情况提高维生素D的补充率,同时增加儿童户外活动,促进学龄前儿童健康。